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Updated: Jan 17, 2026

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
Published on: February 17, 2023
Engineered prime editors with minimal genomic errors
Vikash P Chauhan1,2, Phillip A Sharp3,4, Robert Langer5,6
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. vpc@mit.edu.
Abstract:
Prime editors make programmed genome modifications by writing new sequences into extensions of nicked DNA 3' ends1. These edited 3' new strands must displace competing 5' strands to install edits, yet a bias towards retaining the competing 5' strands hinders efficiency and can cause indel errors2. Here we discover that nicked end degradation, consistent with competing 5' strand destabilization, can be promoted by Cas9-nickase mutations that relax nick positioning. We exploit this mechanism to engineer efficient prime editors with strikingly low indel errors. Combining this error-suppressing strategy with the latest efficiency-boosting architecture, we design a next-generation prime editor (vPE). Compared with previous editors, vPE features comparable efficiency yet up to 60-fold lower indel errors, enabling edit:indel ratios as high as 543:1.
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